Plant derived inhibitor Sulforaphane in combinatorial therapy against therapeutically challenging Pancreatic Cancer.
Anticancer Agents Med Chem. 2016 Jun 6. Epub 2016 Jun 6. PMID: 27281367
Shabir Ahmad Ganai
Pancreatic cancer is one of the most aggressive human cancers and is expected to surpass breast cancer to become the third chief cause of cancer-related deaths in the United States. While conventional treatment approaches such as surgery and classic chemotherapy have slightly improved the relative five year survival rate to 8% yet it is the lowest survival rate for any major cancer emphasizing the desperate need of more effective and well tolerated therapies to reverse the poor prognosis of the defined neoplasm. Aberrant expression of histone deacetylase (HDAC) enzymes has been implicated in pancreatic cancer signalling and the inhibitors of these enzymes namely HDAC inhibitors (HDACi) are the novel agents which are currently being tested. These inhibitors modulate both histone and non-histone proteins and have shown multiple biological effects including cell cycle arrest, differentiation and apoptosis in several cancer models. In this review we focus on plant derived HDACi Sulforaphane as a promising molecule against pancreatic cancer therapy. Moreover, we discuss the distinct molecular mechanisms triggered by this defined inhibitor to exert cytotoxic effect in various pancreatic cancer models. Finally we describe thoroughly the combinatorial therapeutic strategy involving Sulforaphane in conjunction with other anticancer agents to tackle therapeutically challenging pancreatic cancers in a safe and effective manner.